The effect of adrenocorticotropic hormone (ACTH) on embryonic chicken gonads

Chicken embryos were exposed to a single dose of adrenocorticotropic hormone (ACTH) on the 15th day of the incubation period. Five days later, the female embryos showed a significant increase in ovarian weight, ovarian thickness and oocyte count. In contrast, the male embryos showed a significant decreased in testicle weight, seminiferous cord diameter and gonocyte number. The opposite response of testes and ovaries is discussed.     

Mutagenic evaluation of the monocyclic aromatic amine N-methylamino-2-nitro-4-N', N'-bis(2-hydroxyethyl)-aminobenzene in the Salmonella typhimurium/mammalian microsome test

The hair-dye component N-methylamino-2-nitro-4-N', N'-bis(2-hydroxyethyl) aminobenzene was investigated for mutagenic activity in Salmonella typhimurium strains TA1535, TA100, TA1537, TA1538 and TA98. The testing was performed in the absence and in the presence of a rat-liver microsomal activation system induced by Aroclor 1254. Our results indicate that N-methylamino-2-nitro-4-N', N'-bis(2-hydroxyethyl)aminobenzene does not induce mutations in Salmonella typhimurium strains, either in the absence or in the presence of the metabolic activation system. The purity of the compound was controlled by utilizing high-pressure liquid chromatography (HPLC) and thin-layer chromatography (TLC).     

Prognostic factors for esophageal squamous cell carcinoma--a population-based study in Golestan Province, Iran, a high incidence area

Golestan Province in northern Iran is an area with a high incidence of esophageal squamous cell carcinoma (ESCC). We aimed to investigate prognostic factors for ESCC and survival of cases in Golestan, on which little data were available. We followed-up 426 ESCC cases participating in a population-based case-control study. Data were analyzed using the Kaplan-Meier method and the Cox proportional hazard models. Median survival was 7 months. Age at diagnosis was inversely associated with survival, but the association was disappeared with adjustment for treatment. Residing in urban areas (hazard ratio, HR?=?0.70; 95% CI 0.54-0.90) and being of non-Turkmen ethnic groups (HR?=?0.76; 95% CI 0.61-0.96) were associated with better prognosis. In contrast to other types of tobacco use, nass (a smokeless tobacco product) chewing was associated with a slightly poorer prognosis even in models adjusted for other factors including stage of disease and treatment (HR?=?1.38; 95% CI 0.99-1.92). Opium use was associated with poorer prognosis in crude analyses but not in adjusted models. Almost all of potentially curative treatments were associated with longer survival. Prognosis of ESCC in Golestan is very poor. Easier access to treatment facilities may improve the prognosis of ESCC in Golestan. The observed association between nass chewing and poorer prognosis needs further investigations; this association may suggest a possible role for ingestion of nass constituents in prognosis of ESCC.     

Regulated Extracellular Choline Acetyltransferase Activity— The Plausible Missing Link of the Distant Action of Acetylcholine in the Cholinergic Anti-Inflammatory Pathway

Acetylcholine (ACh), the classical neurotransmitter, also affects a variety of nonexcitable cells, such as endothelia, microglia, astrocytes and lymphocytes in both the nervous system and secondary lymphoid organs. Most of these cells are very distant from cholinergic synapses. The action of ACh on these distant cells is unlikely to occur through diffusion, given that ACh is very short-lived in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), two extremely efficient ACh-degrading enzymes abundantly present in extracellular fluids. In this study, we show compelling evidence for presence of a high concentration and activity of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT) in human cerebrospinal fluid (CSF) and plasma. We show that ChAT levels are physiologically balanced to the levels of its counteracting enzymes, AChE and BuChE in the human plasma and CSF. Equilibrium analyses show that soluble ChAT maintains a steady-state ACh level in the presence of physiological levels of fully active ACh-degrading enzymes. We show that ChAT is secreted by cultured human-brain astrocytes, and that activated spleen lymphocytes release ChAT itself rather than ACh. We further report differential CSF levels of ChAT in relation to Alzheimer’s disease risk genotypes, as well as in patients with multiple sclerosis, a chronic neuroinflammatory disease, compared to controls. Interestingly, soluble CSF ChAT levels show strong correlation with soluble complement factor levels, supporting a role in inflammatory regulation. This study provides a plausible explanation for the long-distance action of ACh through continuous renewal of ACh in extracellular fluids by the soluble ChAT and thereby maintenance of steady-state equilibrium between hydrolysis and synthesis of this ubiquitous cholinergic signal substance in the brain and peripheral compartments. These findings may have important implications for the role of cholinergic signaling in states of inflammation in general and in neurodegenerative disease, such as Alzheimer’s disease and multiple sclerosis in particular.     

Phylogenetic Relatedness of Circulating HIV-1C Variants in Mochudi,Botswana

Background

Determining patterns of HIV transmission is increasingly important for the most efficient use of modern prevention interventions. HIV phylogeny can provide a better understanding of the mechanisms underlying HIV transmission networks in communities.

Methods

To reconstruct the structure and dynamics of a local HIV/AIDS epidemic, the phylogenetic relatedness of HIV-1 subtype C env sequences obtained from 785 HIV-infected community residents in the northeastern sector of Mochudi, Botswana, during 2010–2013 was estimated. The genotyping coverage was estimated at 44%. Clusters were defined based on relatedness of HIV-1C env sequences and bootstrap support of splits.

Results

The overall proportion of clustered HIV-1C env sequences was 19.1% (95% CI 17.5% to 20.8%). The proportion of clustered sequences from Mochudi was significantly higher than the proportion of non-Mochudi sequences that clustered, 27.0% vs. 14.7% (p = 5.8E-12; Fisher exact test). The majority of clustered Mochudi sequences (90.1%; 95% CI 85.1% to 93.6%) were found in the Mochudi-unique clusters. None of the sequences from Mochudi clustered with any of the 1,244 non-Botswana HIV-1C sequences. At least 83 distinct HIV-1C variants, or chains of HIV transmission, in Mochudi were enumerated, and their sequence signatures were reconstructed. Seven of 20 genotyped seroconverters were found in 7 distinct clusters.

Conclusions

The study provides essential characteristics of the HIV transmission network in a community in Botswana, suggests the importance of high sampling coverage, and highlights the need for broad HIV genotyping to determine the spread of community-unique and community-mixed viral variants circulating in local epidemics. The proposed methodology of cluster analysis enumerates circulating HIV variants and can work well for surveillance of HIV transmission networks. HIV genotyping at the community level can help to optimize and balance HIV prevention strategies in trials and combined intervention packages.     

Impact of a Labour Disruption Affecting Local Public Health on the Incidence of Chlamydia Infections in Toronto

Introduction

Labour disruptions that interrupt services can be a natural experiment to examine the effect of halting a program. A five-week municipal labour disruption in Toronto during the summer of 2009 provided an opportunity to investigate the impact of reduced sexual health services.

Methods

We examined the incidence of reported chlamydia in Toronto during the five years (2004–2008) preceding the labour disruption and during the periods just before, during, and after the labour disruption. Comparisons of actual reports for 2009 were made to immediately adjacent periods around the labour disruption, to historical trends and to forecasted rates. Interrupted time series analysis was used to test for significant differences in the trend of reported chlamydia incidence.

Results

There was no significant difference in the trend of reported chlamydia incidence around the time of the strike. However, there was a small but significant increase in the incidence of reported chlamydia, particularly among females under 25 years old immediately following the labour disruption. The reported incidence for this group was higher than would be expected based on annual increases and projected seasonal trends.

Conclusions

There was a small increase in incidence of reported cases of chlamydia for certain groups that went beyond what is expected during the time immediately following the labour disruption. While causation cannot be implied from our ecological study, public health services may play a role in the control of sexually transmitted infections, even in the short-term. This underscores the need for future work to understand whether the changes observed can be attributed to the absence of these services.     

Novel Jojoba Oil-Based Emulsion Gel Formulations for Clotrimazole Delivery

Jojoba oil-based emulgel formulations were prepared using different concentrations of various gelling agents, such as hydroxypropyl methylcellulose (HPMC) and Carbopol 934 P and combination of both. The prepared emulgels were physically evaluated for their stability after temperature cycle test, centrifugation and long-term shelf storage for 1 year at room temperature. The in vitro release at 37°C was studied to define the effect of the concentration and type of the gelling agent. A comparison between the formulated emulgels and two commercially available products, Candistan® and Canesten® creams, was carried out to judge their efficacy and stability. The prepared emulgels exhibited non-Newtonian shear thinning behavior with little or no thixotropy. Four emulgels showed excellent stability as they demonstrated consistent rheological model under different treatment conditions. The in vitro release test showed variation in the extent of percent drug released. The drug release from the commercial preparation was lower than some of the prepared emulgel formulae. One formula containing combination of the two gelling agents (HPMC and Carbopol 934 P), showed excellent stability and high extent of clotrimazole release was microbiologically evaluated against Candida albicans using cylinder and plate method. The selected formula showed superior antimycotic activity compared to the commercially available formulation. Further in vivo animal studies for the obtained stable formula is recommended.